Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88-plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five-protein biomarker signature for colorectal cancer detection.

Department of Biology Institute of Molecular Systems Biology ETH Zurich Zurich Switzerland

Department of Biology Institute of Molecular Systems Biology ETH Zurich Zurich Switzerland Faculty of Science University of Zurich Zurich Switzerland

Department of Computer Science Institute for Machine Learning ETH Zurich Zurich Switzerland

Department of Statistics Purdue University West Lafayette IN USA

Department of Statistics Purdue University West Lafayette IN USA Department of Computer Science Purdue University West Lafayette IN USA College of Science and College of Computer and Information Science Northeastern University Boston MA USA

Department of Surgery University Hospital in Olomouc Olomouc Czech Republic

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

EMBO Mol Med. 7:1153. PubMed

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Non-invasive prognostic protein biomarker signatures associated with colorectal cancer